Association analysis of single-nucleotide polymorphisms around serotonin transporter gene and bipolar affective disorder in Taiwan.

• Main Authors: Hui-Chun Wang, 王惠君
• Other Authors: H. Sunny Sun
• Format: Others
• Language: en_US
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/m6bb2u

碩士 === 國立成功大學 === 分子醫學研究所 === 90 === Bipolar affective disorder (BPD), also known as manic-depressive psychosis is the major mental illness after major depression. Little is known about the underlying causes of BPD, the lifetime prevalence has estimated about 0.5% to 1% in various populations. Twin, family pedigree and adoption studies all suggested a strong genetic component for BPD. Serotonin (also known as 5-hydroxytryptamine, 5-HT) is a key neurotransmitter in the central and peripheral nervous system and contributes to various physiological functions such as motor activity, food intake, sleep, reproductive activity and emotion. Genes involved in serotonin transmission and metabolic pathways thus are good candidates for studying their involvement in BPD pathogenesis. Serotonin transporter gene (SLC6A4, a member of solute carrier family) consists of 14 exons spanning about 31 kb on chromosome 11q11.1-11.2 and responds for re-uptaking serotonin into presynaptic terminal thus fine-tuning of brain serotonergic neurotransmission. Serotonin transporter has been the primary target for developing therapeutic medicine for the treatment of depression, panic disorder and other psychiatric disorder. Previous studies have indicated that the 5HTTLPR (a 44 bp insertion/deletion polymorphism in the promoter region of the SLC6A4 gene) alters the gene expression thus suggesting a genetic susceptibility factor for BPD. In addition, our preliminary study also demonstrated that 5HTTVNTR (a variable number of tandem repeat in intron 2 region of the SLC6A4 gene) has associated with BPD in Taiwan. To further analyze the role of gene in the etiology of BPD, 10 markers including 5HTTLPR, 5HTTVNTR and 8 single nucleotide polymorphisms (SNPs) within 60 kb interval surrounding the SLC6A4 gene were selected to study the association with BPD in Taiwan. Three fluorescent-based approaches for SNP genotyping have been used in this study. Among these markers, two SNPs were found not informative in Taiwanese population and eight polymorphic markers have been analyzed by classical chi-square test as well as haplotype analysis. No association can be obtained between all SLC6A4 markers and BPD. In addition, significant linkage disequilibrium (LD) was obtained among 8 markers but not between markers and putative disease loci by using the EH program. This study demonstrates that the SLC6A4 gene may not play an important role in BPD etiology and suggest the other candidate genes different from Caucasian may be involved. Besides, the epistatic interaction effect of SLC6A4 with others factors still cannot be excluded and more analysis will be necessary to formulate the serotonin transporter in BPD pathogenesis.